1. Field of the Invention
This invention relates to the dimesylate salt of cis-1-(3-ethoxyphenyl)-1-(4-phenylpiperazin-1-yl)-4-methyl-cyclohexane (compound I) which selectively binds to mammalian Neuropeptide Y receptors. This invention also relates to pharmaceutical compositions comprising compound I. It further relates to the use of compound I and compositions containing compound I in treating physiological disorders associated with an excess of neuropeptide Y, especially eating disorders and certain cardiovascular diseases.
2. Description of the Related Art
Neuropeptide Y, a peptide first isolated in 1982, is widely distributed in the central and peripheral neurons and is responsible for a multitude of biological effects in the brain and the periphery. Various animal studies have shown that activation of Neuropeptide Y.sub.1 receptors is related to vasoconstriction, Wahlestedt et al., Regul. Peptides, 13: 307-318 (1986), McCauley and Wesffall, J. Pharmacol. Exp. Ther. 261: 863-868 (1992), and Grundemar et al., Br. J. Pharmacol. 105: 45-50 (1992); and to stimulation of consummatory behavior, Flood and Morley, Peptides, 10: 963-966 (1989), Leibowitz and Alexander, Peptides, 12: 1251-1260 (1991), and Stanley et al., Peptides, 13: 581-587 (1992).
Grundemar and Hakanson, TiPS, May 1994 Vol. 15!, 153-159, state that, in animals, Neuropeptide Y is a powerful stimuli of food intake, and an inducer of vasoconstriction leading to hypertension. They further point out that low levels of Neuropeptide Y is associated with loss of appetite. These reports clearly indicate that compounds that inhibit the activity of this protein will reduce hypertension and appetite in animals.
The dihydrochloride salt of cis-1-(3-ethoxyphenyl)-1-(4-phenylpiperazin-1-yl)-4-methyl-cyclohexane is described in International Application PCT/US95/14472 which is published as WO 96/14307. The disclosure of the International Application is hereby incorporated herein by reference.